Abstract Pharmacotherapy options for alcohol use disorders remain limited, with only three FDA approved compounds (disulfiram, naltrexone and acamprosate). Recent studies highlight the potential for medications used for the treatment of other indications to be useful in helping patients reduce drinking. Study of additional agents, particularly those that act through novel mechanisms, is needed to expand the range of pharmacotherapy options for alcohol use problems. Additionally, identification of individual subject level predictors of efficacy are needed to better personalize pharmacotherapy treatment recommendations. Extensive preclinical studies indicate that neuroactive steroids mediate important effects of alcohol and support the examination of neuroactive steroid modulators as treatment options for alcohol use disorders (AUD). Dutasteride, a widely prescribed medication for benign prostatic hypertrophy and androgenic hair loss, blocks a key step in the production of neuroactive steroids and represents a promising candidate for treatment of AUD. Interim analysis from the first 12-week RCT of dutasteride for AUD in a sample of male heavy drinkers indicates that dutasteride is well tolerated in alcoholics and has efficacy in helping subjects reduce drinking. Results suggest that dutasteride may be particularly helpful for patients with baseline negative mood or are carriers of a stress-reactive allele of a chaperone protein, FKBP5, involved in regulation of glucocorticoid, androgen and progesterone receptor function. This 24-week treatment study will use an innovative step therapy randomized placebo controlled design to examine the safety and efficacy of dutasteride to reduce drinking among a sample of 190 treatment seeking men and women with hazardous levels of alcohol use. At 12-weeks placebo non-responders will transition to dutasteride and dutasteride non-responders will transition to naltrexone, an FDA approved medication with demonstrated efficacy for reducing heavy drinking. Baseline measures of anxiety and perceived life stress will be examined separately and in conjunction with stress resilient vs. reactive genotypes of FKBP5 as predictors of dutasteride treatment efficacy.